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异种移植中亚临床及临床试验与免疫抑制疗法的进展

Advances in Subclinical and Clinical Trials and Immunosuppressive Therapies in Xenotransplantation.

作者信息

Xing Kai, Chang Yuan, Jia Hao, Song Jiangping

机构信息

Department of Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Xenotransplantation. 2025 May-Jun;32(3):e70053. doi: 10.1111/xen.70053.

Abstract

Organ transplantation remains the foremost effective intervention for end-stage organ failure. Nevertheless, the scarcity of donors has resulted in prolonged waiting times for countless patients globally. The advent of xenografts presents a promising solution to the organ shortage crisis. Although the utilization of xenografts has a long history, it is only in recent years that breakthroughs in genetically modified pigs have rendered successful xenotransplantation a feasible option. In the past 4 years, numerous subclinical and clinical trials have involved xenotransplantation from genetically modified pigs to humans. However, the outcomes have been disappointing, necessitating a reassessment of basic and preclinical research to address the emerging challenges. Furthermore, immunosuppressive therapies remain essential in xenotransplantation. The range of immunosuppressive agents, encompassing traditional immunosuppressants and monoclonal antibodies such as anti-CD154/CD40 monoclonal antibodies, exhibits considerable diversity. However, the most effective drug combination for achieving optimal efficacy remains elusive. This review will offer a succinct overview of the results from recent clinical and subclinical xenotransplantation trials. Moreover, it will highlight recent advancements in immunosuppressive strategies and discuss potential future research directions in this field.

摘要

器官移植仍然是治疗终末期器官衰竭最有效的干预手段。然而,供体的稀缺导致全球无数患者的等待时间延长。异种移植的出现为器官短缺危机提供了一个有前景的解决方案。尽管异种移植的应用历史悠久,但直到近年来,转基因猪的突破才使成功的异种移植成为一个可行的选择。在过去4年里,许多亚临床和临床试验都涉及从转基因猪到人类的异种移植。然而,结果令人失望,这就需要重新评估基础研究和临床前研究,以应对新出现的挑战。此外,免疫抑制疗法在异种移植中仍然至关重要。免疫抑制剂的范围很广,包括传统免疫抑制剂和单克隆抗体,如抗CD154/CD40单克隆抗体,种类繁多。然而,实现最佳疗效的最有效药物组合仍然难以确定。本综述将简要概述近期临床和亚临床异种移植试验的结果。此外,还将重点介绍免疫抑制策略的最新进展,并讨论该领域未来潜在的研究方向。

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